Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Deletion of self-reactive T cells before entry into the thymus medulla

Abstract

The thymus is important in the differentiation of bone marrow-derived precursor cells into functional T cells; humoral factors1–4, as well as physical interactions with nurse cells 5, dendritic cells and epithelial cells6–8, are thought to be instrumental in this process. Thymic lymphocytes mature during their migration from the cortical to the medullary region of the thymus9–11, when they undergo phenotypic changes that include the acquisition of T-cell antigen receptors12–13, hormone receptors1–14, 15and differentiation antigens16. Cortical T cells are thus mostly CD4+CD8+, whereas medullary T cells are either CD4+CD8 or CD4CD8+ (refs 6, 16 and 17). During this period T cells are subjected to two types of repertoire selection: all T cells recognizing self-MHC with low affinity18 may be preferentially amplified (positive selection), and in a second step T cells with high-affinity receptors for self-MHC determinants plus self antigens are eliminated (negative selection). We have described two monoclonal antibodies19 specific for the Vβ6 gene segment of the α/βheterodimeric T-cell antigen receptor and have shown that most CD4+/Vβ6+ T cells recognize the Mlsa antigenic determinant but not Mlsb (ref. 20; similar results have been reported for Vβ8.1 and Mlsa (ref. 21). In both situations, tolerance to Mlsa correlated in an MHC-dependent fashion with absence of Vβ6 or Vβ8.1 T-cell antigen receptor expressing T cells in the periphery. We show here by immunostaining of thymus cryosections and cytofluorometric analysis that Vβ6-expressing cortical T cells are present at high density in both Mlsa and Mlsb mice, but do not enter the medullary region of Mlsa animals.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Howe, R. C., Lowenthal, J. W. & MacDonald, H. R. J. Immun. 137, 3195–3200 (1986).

    CAS  PubMed  Google Scholar 

  2. Palacios, R., Sideras, P. & von Boehmer, H. EMBO J. 6, 91–95 (1987).

    Article  CAS  Google Scholar 

  3. Goldstein, A. L. & Low, T. L. K. Prog. Immun. 5, 1417–1427 (1983).

    Google Scholar 

  4. Bach, J. F. Prog. Immun. 5, 1563–1579 (1983).

    Google Scholar 

  5. Wekerle, H., Ketelsen, U. P. & Ernst, M. J. exp. Med. 151, 925–944 (1980).

    Article  CAS  Google Scholar 

  6. Longo, D. L. & Schwartz, R. H. Nature 287, 44–45 (1980).

    Article  ADS  CAS  Google Scholar 

  7. Kyewski, B. A., Fathman, C. G. & Rouse, R. V. J. exp. Med. 163, 231–246 (1986).

    Article  CAS  Google Scholar 

  8. Kyewski, B. A., Fathman, C. G. & Kaplan, H. S. Nature 308, 196–199 (1984).

    Article  ADS  CAS  Google Scholar 

  9. Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 317, 811–813 (1985).

    Article  ADS  CAS  Google Scholar 

  10. Farr, A. G., Anderson, S. K., Marrack, P. & Kappler, J. W. Cell 43, 543–550 (1985).

    Article  CAS  Google Scholar 

  11. Weissman, I. L. J. exp. Med. 126, 291–304 (1967).

    Article  CAS  Google Scholar 

  12. Budd, R. C. et al. J. exp. Med. 166, 577–582 (1987).

    Article  CAS  Google Scholar 

  13. von Boehmer, H., Karjalainen, K., Pelkonen, J., Borgulya, P. & Rammensee, H. G. Immunol. Rev. 101, 21–37 (1988).

    Article  CAS  Google Scholar 

  14. Lugo, J. P. et al. J. exp. Med. 161, 1048–1062 (1985).

    Article  CAS  Google Scholar 

  15. Lowenthal, J. W., Howe, R. C., Ceredig, R. & MacDonald, H. R. J. Immun. 137, 2579–2584 (1986).

    CAS  PubMed  Google Scholar 

  16. Scollay, R., Bartlett, P. & Shortman, K. Immunol. Rev. 82, 79–103 (1984).

    Article  CAS  Google Scholar 

  17. Crispe, I. N., Moore, M. W., Husmann, L. A., Smith, L. & Bevan, M. J. Nature 329, 336–339 (1987).

    Article  ADS  CAS  Google Scholar 

  18. Zinkernagel, R. M. et al. J. exp. Med. 147, 882–896 (1978).

    Article  CAS  Google Scholar 

  19. Payne, J. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  20. MacDonald, H. R. et al. Nature 332, 40–45 (1988).

    Article  ADS  CAS  Google Scholar 

  21. Kappler, J. W., Staerz, U. D., White, J. & Marrack, P. Nature 332, 35–40 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Haskins, K. et al. J. exp. Med. 157, 1149–1169 (1984).

    Article  Google Scholar 

  23. Behlke, M. A. et al. J. exp. Med. 165, 257–262 (1987).

    Article  CAS  Google Scholar 

  24. Cristanti, A., Colantoni, A., Snodgrass, R. & von Boehmer, H. EMBO J. 5, 2837–2843 (1986).

    Article  CAS  Google Scholar 

  25. Sim, G. K. & Augustin, A. A. Cell 42, 89–92 (1985).

    Article  CAS  Google Scholar 

  26. Barclay, A. N. & Mayrhofer, G. J. exp. Med. 153, 1666–1671 (1981).

    Article  CAS  Google Scholar 

  27. Sprent, J., Lo, D., Gao, K. E. & Ron, Y. Immunol. Rev. 101, 173–190 (1988).

    Article  CAS  Google Scholar 

  28. Kyewski, B. A., Momburg, F. & Schirrmacher, V. Eur. J. Immun. 17, 961–967 (1987).

    Article  CAS  Google Scholar 

  29. MacDonald, H. R., Hengartner, H. & Pedrazzini, T. Nature 335, 174–176 (1988).

    Article  ADS  CAS  Google Scholar 

  30. Fowlkes, B. J., Schwartz, R. H. & Pardoll, D. N. Nature 334, 620–623 (1988).

    Article  ADS  CAS  Google Scholar 

  31. Duvall, E. & Wyllie, A. H. Immun. Today 7, 115–119 (1986).

    Article  CAS  Google Scholar 

  32. MacDonald, H. R., Blanc, C., Lees, R. L. & Sordat, B. J. Immun. 136, 4337–4339 (1986).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hengartner, H., Odermat, B., Schneider, R. et al. Deletion of self-reactive T cells before entry into the thymus medulla. Nature 336, 388–390 (1988). https://doi.org/10.1038/336388a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/336388a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing